18-23305164-C-T

Variant names:

• chr18-23305164-C-T
• rs12326518
• NM_032933.6:c.830+4516G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032933.6(SLC35D4):​c.830+4516G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,074 control chromosomes in the GnomAD database, including 20,870 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (20870 hom., cov: 33)
• Consequence: SLC35D4 NM_032933.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 7 publications found

Genes affected

SLC35D4 (HGNC:31723): (transmembrane protein 241) Predicted to enable antiporter activity. Predicted to be involved in carbohydrate transport and transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032933.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35D4	NM_032933.6	MANE Select	c.830+4516G>A		intron	N/A	NP_116322.3
	SLC35D4	NM_001318834.2		c.467+4516G>A		intron	N/A	NP_001305763.1
	SLC35D4	NR_134875.2		n.890+4516G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM241	ENST00000383233.8	TSL:1 MANE Select	c.830+4516G>A		intron	N/A	ENSP00000372720.3	Q24JQ0-1
	TMEM241	ENST00000542162.5	TSL:1	c.*495+4516G>A		intron	N/A	ENSP00000440152.2	F5GXY7
	TMEM241	ENST00000473688.5	TSL:1	n.*301+4516G>A		intron	N/A	ENSP00000431584.1	Q24JQ0-2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79045 AN: 151956 Hom.: 20856 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.520 AC: 79103 AN: 152074 Hom.: 20870 Cov.: 33 AF XY: 0.521 AC XY: 38689 AN XY: 74330

African (AFR) AF: 0.459 AC: 19029 AN: 41468

American (AMR) AF: 0.454 AC: 6928 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2017 AN: 3472

East Asian (EAS) AF: 0.428 AC: 2212 AN: 5172

South Asian (SAS) AF: 0.606 AC: 2918 AN: 4818

European-Finnish (FIN) AF: 0.557 AC: 5884 AN: 10562

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38320 AN: 67986

Other (OTH) AF: 0.531 AC: 1123 AN: 2114

Alfa AF: 0.542 Hom.: 42045

Bravo AF: 0.505

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.2
DANN	Benign	0.65
PhyloP100		0.098
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12326518; hg19: chr18-20885128;